Practical User Guide for Electronic Application Forms (eaf) for human and veterinary medicinal products in the EU

Transcription

1 ` 10 August 2018 Practical User Guide for Electronic Application Forms (eaf) for human and veterinary medicinal products in the EU Version Page 1 of 80

2 Note to readers This guidance reflects the current state of knowledge and is subject to future updates to take new information on-board. Therefore, it is important that comments are fed back to the eaf User Group by e- mail EMA IT service desk ( Screenshots in this document have been, in most cases taken using eaf version In some cases, this guidance will still use screenshots based on earlier versions. It is not possible to match this guidance document with one exact version of the eaf. However, information about new functionalities or changes are in the up to date release notes at: Page 2 of 80

3 Document History Change Record Version Author(s) Comments 1.0 eaf User Group This document has been prepared by the sub-group on guidance and information of the eaf User Group in collaboration with CMDh and CMDv eaf User Group First draft for revision, made the document in line with reported corrections, improved consistency with the Q&A on eaf and aligned with changes of the eafs version eaf User Group Indicating acceptance of an image of a text snippet for EMA, additional advice for optimising the PDF file for ectd purpose, minor editorial changes after review 1.2 eaf Sub-Group on Guidance Update of the guidance to include new features of version 1.20 as well as to improve several sections based on user comments. 1.3 eaf Sub-Group on Guidance Consolidation of review comments eaf Sub-Group on Guidance Deleting the note in section pointing to a workaround not meaningful eaf Sub-Group on Guidance Update based on eaf v (Screenshots updated as necessary, advice on button Add All for member states in MAA hum/vet and REN), correction of link to EMA IT service desk eaf Sub-Group on Guidance Clean version for publication 1.6 EMA Updated to reflect eaf v EMA / eaf Sub-Group on Guidance Updated to reflect eaf v and the NtA changes triggering the updated version of the eaf eaf Sub-Group on Guidance Including clarification on section Reviewers Version Name Organisation 1.0 Representatives of NCA and EMA eaf Full Group, Representatives of NCA and EMA CMDh, Page 3 of 80

4 Version Name Organisation Representatives of NCA and EMA CMDv 1.1 Representatives of NCA and EMA eaf Full Group, 1.2 Representatives of NCA and EMA eaf Full Group, CMDh and CMDv, esub CMB 1.7 Representatives of NCA and EMA eaf Full Group, CMDh and CMDv, esub CMB Distribution Version Distributed to Method of distribution 1.0 General public Published on the EMA esubmission website 1.1 General public Published on the EMA esubmission website 1.4 General public Published on the EMA esubmission website 1.5 General public Published on the EMA esubmission website 1.6 General public Published on the EMA esubmission website 1.7 General public Published on the EMA esubmission website General public Published on the EMA esubmission website Entering operation Version Date Comments 1.0 July 2015 This guidance document should always be read in conjunction with the respective regulatory guidance documents on human and veterinary medicinal products. In parallel a Q&A document is available providing quick up-to-date additional information regarding usage of eafs. 1.1 October 2015 This is an interim update. A next update will follow once the eaf version 1.19 is published. 1.4 June 2016 This is an interim update. Further updates are expected based on user feedback once version 1.20 is published. 1.5 October 2016 Updated version based on eaf v December 2017 Updated version based on eaf v July 2018 Updated version based on eaf v August 2018 Updated version based on version 1.7 Page 4 of 80

5 Contents Note to readers... 2 Document History... 3 Change Record... 3 Reviewers... 3 Distribution... 4 Entering operation... 4 Contents... 5 Purpose and general technical rules... 9 Purpose of this document... 9 Referential term change request processes... 9 Access to the forms and news on updates Adobe Reader requirements and IT security settings Opening the form Navigating the forms Integration of the forms into dossier Export of XML data Import of the XML data Update of the XML data Data fields and formats Providing OMS organisation details to auto-populate address fields File Naming Convention Signature Saving the form MAA FORM (human) Administrative Data Declaration and Signature Product (Invented) name Pharmaceutical form Strength(s) Active Substance(s) Base/Active moiety Applicant Person confirming fees will be/ have been paid, on behalf of the Applicant Type of application This application concerns A Centralised Procedure A Mutual Recognition Procedure A Decentralised Procedure A National Procedure Orphan Medicinal Product Information (human only) Page 5 of 80

6 1.3. Application for a change to existing marketing authorisation leading to an extension as referred to in Annex I of Regulation (EC) no 1234/2008, or any national legislation, where applicable? This application is submitted in accordance with the following article in Directive 2001/83/EC as amended Consideration of this application requested under the following article of Directive 2001/83/EC or Regulation (EC) No 726/ Requirements according to Regulation (EC) N 1901/2006 ( Paediatric Regulation ) Marketing Authorisation Application Names(s) and ATC code Proposed (invented) name of the medicinal product in the European Union / Member State/Iceland/Lichtenstein/ Norway Active substance(s) Pharmacotherapeutic group Strength, pharmaceutical form, route of administration, container and pack sizes Strength and pharmaceutical form (use current list of standard terms European Pharmacopeia) Route(s) of administration (current list standard terms - European Pharmacopoeia) Container, closure and administration device(s) Medical Devices Legal status Marketing authorisation holder / contact persons / company Proposed responsible marketing authorisation holder/person Person/company authorised for communication on behalf of the applicant during the procedure Person/company authorised for communication Summary of the applicant pharmacovigilance system Manufacturers Authorised manufacturer(s) (or importer(s)) responsible for batch release in the EEA Manufacturer(s) of the medicinal product and site(s) of manufacture Manufacturer(s) of the active substance(s) and site(s) of manufacture Contract companies used for clinical trial(s) (including bioavailability and bioequivalence studies) included in the application or used for the validation of blood product manufacturing processes Quantitative and Qualitative Composition Qualitative and Quantitative composition in terms of the active substance(s) and the excipient(s) List of materials of animal and/or human origin contained/ used in the manufacturing process of the medicinal product? Is an EMEA certificate for a Plasma Master File (PMF) issued or submitted in accordance with Directive 2001/83/EC Annex I, Part III, being used for this MAA? Does the medicinal product contain or consist of Genetically Modified Organisms (GMOs) within the meaning of Directive 2001/18/EC? Scientific advice Was there formal scientific advice(s) given by EMA for this medicinal product? Was there scientific advice(s) given by Member State(s) for this medicinal product? Page 6 of 80

7 4. Other marketing authorisation applications Annexed documents (where appropriate) MAA FORM (veterinary) Administrative data Declaration and signature Type of application This application concerns A Centralised Procedure A Mutual Recognition Procedure A Decentralised Procedure A National Procedure Is this an application for a change to your existing marketing authorisation leading to an extension as referred to in Annex I of Regulation (EC) NO 1234/2008, or any national legislation, where applicable? This application is submitted in accordance with the following articles in Directive 2001/82/EC MRL status (only for food-producing species) Consideration of this application is also requested under the following article in Directive 2001/82/EC or Regulation (EC) No 726/ Marketing authorisation application particulars Name(s) and ATC vet code and target species Proposed (invented) name of the veterinary medicinal product in the European Union / Member State/Iceland/Lichtenstein/ Norway Active substance(s) Pharmacotherapeutic group (Please use current ATC vet code) Target species Strength, pharmaceutical form, route of administration, container and pack sizes Strength and pharmaceutical form (use current list of standard terms European Pharmacopeia) Route(s) of administration (use current list of standard terms - European Pharmacopoeia) Container, closure and administration device(s), including description of material from which it is constructed. (use current list of standard terms - European Pharmacopoeia) Legal status Marketing authorisation holder / contact persons / company Manufacturers Quantitative and qualitative composition Qualitative and Quantitative composition in terms of the active substance(s) and the excipient(s) List of materials of animal and/or human origin contained or used in the manufacturing process of the medicinal product? Does the veterinary medicinal product contain or consist of Genetically Modified Organisms (GMOs) within the meaning of Directive 2001/18/EC? Scientific advice Was there formal scientific advice(s) given by CVMP for this veterinary medicinal product? Was a scientific recommendation(s) given by Member State(s) for this veterinary medicinal product? Page 7 of 80

8 4. Other marketing authorisation applications Annexed documents (where appropriate) VARIATION FORM Application for variation to a marketing authorisation Products concerned by this application Types(s) of changes (s) Present and proposed section text fields Present and proposed section address details a Type IB and Type II variations new indications orphan medicinal product information b Type IB and Type II variations Paediatric Requirements c Type II variations Extended data exclusivity/market protection Annexed documents (where appropriate) Declaration of the applicant Signature RENEWAL FROM Application form for renewal of a marketing authorisation Approved manufacturers Quantitative and qualitative composition in terms of the active substance(s) and the excipient(s) Documents appended to this application Declaration and Signature Page 8 of 80

9 Purpose and general technical rules The following pages provide general technical information in regard to all electronic application forms. Additional information related to the specific application forms is provided in separate sections. Purpose of this document As part of a submission package, it is mandatory for all (Human and Veterinary) submissions in EU Member States to use the electronic application form. The paper MS Word application forms are no longer provided by Notice to Applicants (NtA). This document provides practical and technical support on the use of the Electronic Application Forms (eafs) for human and veterinary medicinal products, and in addition to the regulatory user guide for the electronic application form for a marketing authorisation which is available for human medicinal products at CMDh and for veterinary medicinal products at CMDv. This document should be read in the context with the regulatory guidance referenced above. Note: Reliable regulatory information must be taken from the (regulatory) user guides of the application form only. A question and answer document is available at to cover anticipated questions relating specifically to the electronic forms. Field level help or tool tips are also available in the eaf by moving the mouse pointer over each field of the electronic forms. Note: If the tooltips are not visible when you hover over the fields in the forms please contact your IT support. The release notes list any new functionality when new versions of the forms become available. It is strongly recommended to review the release notes each time a new version of the forms is available. Information is also available relating to the use of the forms in the release notes, for example some workaround solutions. If you encounter an issue with a specific field, please refer to the Known Issues section in the release notes for the specific form here on the esubmission website. Raise any new issues with the EMA Service Desk. If the information cannot be included in the form, please review any workaround solutions provided in the release notes, or use an annex. In case of any further technical queries, please contact the EMA Service Desk Referential term change request processes In case of a missing term and as a general rule, in order to complete an eaf, use the RMS Change Request processes as outlined in the Referential Management Services (RMS) operating model document. Please submit a request using the SPOR Portal: Provide as much supporting documentation as possible (e.g. name of the product concerned, SmPC, etc.). Please note you need to be registered with SPOR prior to submission of change requests: The user guide for managing referential and organisation data in eaf is available here. Page 9 of 80

10 If you need to request a missing substance in order to complete an eaf, please submit a request for substance insertion with the corresponding SmPC to the EMA Service Desk portal - Access to the forms and news on updates The use of the electronic application form has become mandatory as of July 1 st, 2015, for the centralised procedure and as of January 1 st, 2016, for all MRP/DCP and national procedures. Technical details are accessible at The latest versions of the respective forms can also be found there. Updates to the electronic application forms are expected to reflect any changes agreed by the European Commission, in consultation with the competent authorities of the Member States and the European Medicines Agency (EMA). Note: Regular updates occur according to release planning. The simplest way to keep up to date with changes to eaf is to subscribe to the eaf RSS feed. For more information about RSS feeds, see The EMA s Guide to RSS. Adobe Reader requirements and IT security settings When opening the eaf for the first time with Adobe Acrobat, Adobe Reader or an Adobe related plug-in the ectd review tool, click Allow content when prompted, then click Trust this document always. To avoid any issues, it is recommended that you (re)install your chosen review tool after any Adobe software related updates. Adobe no longer supports version 9 or earlier, so we strongly advise to upgrade Adobe Acrobat/Reader to the latest version. Please keep updated about Adobe supported versions. The minimum specification to use eaf is Adobe Reader/Acrobat version 10 or above. If you wish to continue using Adobe Acrobat 9 and eafs are working fine with it then do so, however should there be any compatibility issues then Adobe is unable to support the EMA. Extensive testing has not been performed using Linux or Mac OS environments, however there are no known issues preventing the use as long as Adobe reader, and an internet connection are accessible. Note: The built-in PDF viewer with Mozilla Firefox and Google Chrome do not support XFA based PDF forms. Guidance to assist with resolving this issue can be found here. If you receive this error message when opening the form the first time click Options and click Trust this document always. Note: If the IT policy of your local organisation prohibits you from making changes to a security setting, contact your local IT service desk and request that they allow access to the following URL: Important: The web services location, managed by the EMA, enables many of the forms fields, searches and drop-down lists to be populated dynamically. Without access, the form cannot be completed. Page 10 of 80

11 Opening the form The eaf forms are connected to a web services and this means they can take longer to open than conventional documents. When a form is opened, lists are loaded from EUTCT and RMS and some have built in business validation rules which can make the forms large although. Drop-down lists are also loaded into the form and when initially opened and this is one of the reasons that the form takes longer time to open. The average response times for how long it takes to open a current version of the eaf depends on the form. The responses are also different for new forms that are being opened directly from the eaf website as opposed to those that have been filled in, locked and submitted by the MAA/MAH. Note: The searchable fields will not work if there is no internet connection (such as Active substance, Excipients and ATC code). Navigating the forms You can jump between different sections of the forms by clicking your mouse on the bold blue section name. When you click to this text you are automatically taken to the Table of Contents section from where you can navigate to any other part of the form. This functionality is limited in the locked forms where the table and contents and all the headers have been greyed out. The return to the Table of Contents will only work if the header is surrounded by dotted line. Page 11 of 80

12 It is also possible to jump back to the respective sections of the form footnote references in the end of the document and back to the relevant section in the form by clicking the section that is surrounded by a dotted line. This functionality is disabled in locked forms. Integration of the forms into dossier Only the final signed PDF created using the electronic forms should be submitted in the relevant part of the dossier. Indeed, the XML data can be extracted from the pdf file. This action will be performed by agencies when receiving the pdf form. Therefore, applicants should refrain from providing the XML data file separately. It is underlined that the forms are secured in such manner that no change can be brought outside filling the field, i.e. no bookmarks or hyperlinks can be added, no merging with other files can be done, no comments can be brought in the pdf file. In addition, it is not allowed to add any attachments/hyperlinks to the document. If the eaf.xml is stored in the CTD (ectd or NeeS) sequence or VNeeS submission, an error during technical validation will be reported. It is of course strongly advised against printing out the form and scanning it in. Important: You must not use the attachment function within the forms to attach supporting documents. Whilst this feature is visible in the Reader/Acrobat window under a paper clip ( ), it should not be used. To avoid confusion, this functionality maybe removed as a future enhancement to the electronic forms. Important: Do not use the bookmarking functionality in PDF as this affects on how the forms are locked and may lead to rejection by receiving agencies. Page 12 of 80

13 Export of XML data The Export XML function allows users to extract the content of the electronic form in the XML (extensible Mark-up Language) file format. This is useful in a number of ways, including: 1. The XML output can be used in other IT systems (for example receiving regulators can use this data to populate their systems). 2. Previously exported XML outputs may be imported into a new version of the form, as long as the underlying.xsd (XML Schema Definition) has not changed in the interim. 3. The XML file is much smaller than the PDF file so may be considered more suitable for archiving. To extract and view the XML do the following: 1. Navigate to the Form Validation page in the PDF, and then click Export XML to create an XML file. 2. To export the full form xml (including the drop-down list cache in the envelope node of the schema), click No when asked Would you like to export just the user entered form data? 3. To extract the user entered data only, click Yes when asked Would you like to export just the user entered form data?. 4. Save the file in your local file system and use your chosen XML file editor to view the data and its structure. Note: You may also use the inbuilt export xml tool in Reader or Acrobat. The procedure to reach the inbuilt function varies in the different major software versions. The common procedure path for Reader 10 is: Extended>Export Data. The export can also be automated although the EMA does not provide a specific tool. Import of the XML data This function mainly used by industry in order to recover and reuse data from a previous eaf into a new one. It is also possible to import XML data in the correct format, if you have previously exported XML data (as long as the underlying.xsd (XML Schema Definition) has not changed in the interim): 1. Navigate to the Form Validation page in the PDF, and click Import XML to open the file system browser to find a previously created XML file. 2. Once the xml is imported, save, close then re-open the form whilst online to refresh the lists. Note: You may also use the built in import xml in Reader or Acrobat to import previously completed form data. Important: Performing this procedure, may overwrite the cached drop-down lists with an older version. To ensure this is resolved, save, close and re-open the form whilst online. This will refresh the lists and overwrite any outdated list content in the form cache. Note: It is possible that some information will be lost when you export and import data from an older version of eaf to a new version due to changes in the form, and underlying schema. However, if you export from unlocked version and import into new version you will be able to change content in the form. When exporting from a locked version of the form you can only make changes in the actual xml and import into the new version. Page 13 of 80

14 Update of the XML data Concerns that the content will not remain the same after a couple of months (and require a print due to modified terms from controlled terms lists) are not justified as the terms will have a version ID which will assure that the display remains the same. In case of updates of the eaf it will be possible to extract the data from the existing version of the form and import the data into the revised version. Most likely, manual correction may have to be done at least if data field types have been changed. When any eafs are opened when connected to the internet, an automatic version check is done to notify the user if a new version of the eaf is available for download. Drop down terms are always updated when opening the form. Click the Update lists button to update the list. To manually check the version of eaf, do the following: 1. Right-click on the body of the form and select Document Properties or on the Acrobat menu bar click: File>Properties (PC keyboard shortcut= CTRL+D). 2. The Document Properties dialog window is displayed. Click the Custom tab to find version information. Note: The NtA revision number of the form on the right hand side reflects the paper form on which the particular electronic form is based on. The version number of the eaf is displayed on the left hand side. Data fields and formats In the form square boxes indicate that multiple choices are possible while round boxes indicate that one choice excludes the other possibilities. Free text fields have been implemented in a number of sections of the forms where no controlled terminology is available. Improvement is ongoing on finding best solution to implement structured data fields throughout the form. In some sections free text fields provide additional options to describe e.g. roles of a manufacturer as long as no controlled terminologies are available. Normally, free text fields in the forms allow only plain text. Only in the table for present and proposed information text in the variation form inclusion of formatted text will be possible (see section 3 of VAR form). Tracked-changes functionality is currently not available in interactive Acrobat forms. The user interface indicates where text fields, data fields or entire sections can be duplicated or eliminated by using + or - buttons. Page 14 of 80

15 eafs are intelligent forms with built in business rules. Some sections are only displayed depending on previous selections. It is not necessary/possible to delete sections which are not required. Once information is entered, the fields remain visible when un-ticking corresponding fields. To reduce the risk of accidental data loss completed sections when completed, are hidden. Data can only be deleted on a field by field basis by users. In some other cases, the values will be deleted when a different selection is chosen in the variations form when you switch between centralised and MR procedures. The pop-up calendar fields allow you to select future months, and years within the form. With the calendar open, click the month/year and select the month/year option from the drop-down menu. Finally, click the day to close the calendar. In some forms there are copy from xx buttons to allow copying information from previous sections to remove the need to re-enter data multiple times. Please provide any proposals for implementation of certain sections/fields, any usability issues of the forms or certain character sets that you would like to see in any future implementation in order to meet your needs. Providing contact & address details Provide contact and address in a consistent way. Given there are a number of these sections required, the eaf provides users with the ability to reuse this data from one section to another. This reduces the need to repeat entry steps. See the example below: There are two ways offered to complete the data fields: You can complete address data line by line manually or select these details from the Organisation Management Service (OMS) by using an appropriate identifier (see over-next sub-section) Manual completing address details Information how the address details must be entered in are provided in the tooltips when you hover over the corresponding field. Page 15 of 80

16 Providing OMS organisation details to auto-populate address fields In order to facilitate entry of the large number of required organisation and address details; eaf is integrated with OMS data. This allows users to search and select organisations from OMS records resulting in the auto-completion of the related address fields. This is to simplify data entry and reduce the number of repetitive manual data entry steps, in addition one of the first integrated system under the Agency SPOR program. In all eafs where there are organisation and address details required (with the exception of CROs & Billing Addresses), users will see the following: after clicking Find Organisation: Page 16 of 80

17 This allows users to search for OMS organisations by using either: A unique Organisation ID\Location ID (OrgID/LocID). This 9 digit unique ID is issued as part of the OMS registration process. Using a combination of both the organisation name and country Once the search is executed, the results are displayed in pipe delimited format with the following details: Language Company Name Address Line 1 City Country Note: The contents and structure is entirely dependent on the data present in OMS; given the early stage of OMS it is likely that not all data will be available as required. If data is missing or corrections are required; these need to be managed through the OMS change management process. Refer to the following link for further information: Page 17 of 80

18 Once the OMS record has been selected all address related fields will be populated with the exception of the telephone, fax & . These details are held in OMS on the company level and the information required in the eaf is required for the procedure specific contact. There is also the possibility to enter previously selected OMS addresses without having to perform a search on each individual entry; further aiding entry of organisation address fields, and can be illustrated as follows: If the service is temporarily unavailable or matching data is not available the following error messages is displayed: Page 18 of 80

19 Proceed and complete the address data manually. File Naming Convention For human medicinal products the file name will be common-form-var.pdf. The variable part should be used as outlined in the file & folder naming convention of the updated ectd validation criteria version 6.1. NeeS validation criteria version 4.1. In case you have to annex parts from the Classification Guideline for variations, this should become part of the var - section, e.g. common-form-annexclassgl.pdf In case of veterinary submissions please consult the respective guidance. Rendering the eaf PDF file for ectd purpose Be aware of the settings for optimising the PDF file in accordance with the ectd specifications. Make sure, that the line Document Processing is ticked on (as highlighted below) to allow full text index with catalogues and managing embedded indexes. Validating the form You can click the Validate Form button on the last page of each of the eafs as soon as you open the document. Once the forms are validated all mandatory fields are highlighted (in yellow or red). Validation can be performed as often as needed. The resulting list will provide links to the respective section where corrections or additional entries are needed. Page 19 of 80

20 If you are providing a separate annex to the application form instead of entering the information directly in a particular mandatory field, enter a space, N/A (not applicable) or a full stop to bypass the current minimum validation requirements. If the field does not allow text/full stop ignore the validation error and note this in the application cover letter. In certain cases, it might not be possible to fill in all mandatory fields in the eafs leaving some form validation errors. If the information required in such fields is provided via an annex for example, or the fact that the information is not available is mentioned in the cover letter this doesn t normally cause any issues during content validation phase. However, if information required in the mandatory section is not filled in and no annex is provided a content validation issue might be triggered and the application cannot be processed. The form validation is simply a feature that enables use of business rules and guides the MAA/MAH to fill in the form correctly to avoid content validation issues once the application has been submitted. The validation errors are not visible in the form after it is locked and signed, however, the number of remaining errors will be displayed in the validation screen of the locked form. Validating the form before entering the data might affect the form performance by making data entry slightly slower consider if you wish to validate the form, to highlight mandatory fields, before you start data entry. Note: Validation rules are imposed to ensure that a good quality submission is enabled for all concerned parties. The validation rules are not linked to ectd, NeeS or VNeeS validation rules and in some cases, for example when separate annex is used, it is acceptable to have validation error in the form which does not lead to business validation issues. Applicants are encouraged to contact EMA technical help EMA IT service desk if currently implemented business rules should be reviewed and/or changed. If you have any questions, comments or proposals for a best practice solution based on your requirements, please send these to EMA IT service desk for consideration. Signature In regard to the requirements of signing the application form, EMA and national competent authorities may have different legal obligations. Consult their respective websites. Additional information will be provided by CMDh and CMDv. Up to now the effect of inserting an image (normally this will be an image of a relevant signature. In addition, an image of a text snippet stating that this form was signed by the person authorised by the applying company can be used as well, (e.g. stating This form was approved/authorized following company policies by [Mr. Nick Name; Head of Reg. Affairs] with authorization to sign. The signature is in file. ) The image is to lock the application form to avoid any further data manipulation. This image will not work as a digital advanced or qualified electronic signature nor can replace requirements of wet signed forms. Brief instructions how to insert an image are contained within the tooltip for all signature fields within the eafs. In order to ensure that the image is displayed accurately, follow the recommendations below: Unit of Measurement Width Height centimetres Inches 5 1 pixels Page 20 of 80

21 Note: Digital signatures (as opposed to scanned signatures) are not currently within the scope of this project. Important note: The inclusion of the signature (image) will lock the form and prevent further data entry. Therefore, the insertion of that image should be the very last step completing the form. It is recommended to save an un-locked version of the form and to execute the validation of the form prior to including the signature image. However, export of the xml file and re-import into a new eaf pdf file will work as well. There is no need to use qualified signatures for eafs submitted to the EMA for Centralised Procedure applications. The eaf does not change the wet signature requirements at the NCAs. Please check the national requirements for wet signatures to avoid validation issues. In DCP/MRP an AF signed by multiple responsible persons is needed for communication with specific Authorities (could be initial submission or renewal or variation). Ideally provide a single contact point. For those NCAs that require multiple contact persons include a separate annex with the contact details. Saving the form The filename format for human submissions is the same as for the paper form and is detailed in the latest version of the EU Module 1 Specification EU Module 1 Specification (Appendix 2: Directory / File Structure for Module 1 (Sequential Number 9)). Also for veterinary submissions the requirements for filenames do not change with introduction of the eaf. The eaf form (.pdf) itself contains the xml data. This document should be included within the CTD structure in folder 1.2. In the VNeeS dossier structure the correct location is in folder 1a- admin-info. Do not include the raw xml extraction separately (see here for more details). It is strongly recommended to save the form before locking the form. You might need to use the unlocked version to update the application form in case of business validation issues when updated application form is requested. In addition, you can re-use the file for e.g. a new variation of the same product. As an alternative and independent from locking the form, you are also able to export the XML data and import them in an empty form and correct or modify the data then. Note: If the form has been locked with a signature image, this image will be exported and imported back. The eaf will remain locked. To save the form, click Save Form at the end of the form or press Ctrl + S. Note that if you have not saved it to a specific location, the Save As option is displayed prompting you to save in a particular folder other than the default location. Note: When a signature file is attached to the eaf it will be locked and no further changes are possible (with the exception of the additional signatory section, where only this section is locked). MAA FORM (human) On the following pages technical information in regard to the human marketing authorization application form is provided. Additional information related to the veterinary form as well as related to the variation and renewal form will be provided in a separate section thereafter. Administrative Data Declaration and Signature A screenshot is provided to illustrate some principles in this section. Page 21 of 80

22 Product (Invented) name The form allows one product name to be provided. In the text field 250 characters can be used. In case of different names and marketing authorisation holders in the concerned member states a separate list needs to be appended to the application form in Annex However, for MAA for MRP/DCP there should be one common application form for each form or strength but for all member states involved. Pharmaceutical form The pharmaceutical form should be described as in the current version of standard terms from the Ph. Eur. provided by the EDQM as also displayed via SPOR RMS controlled vocabulary list. Only the full term should be mentioned (not the short term). The dropdown includes the pharmaceutical forms described in the Standard terms published in the European Pharmacopoeia that provides standardised nomenclatures and quality standards for medicinal substances and products ( Page 22 of 80

23 Keying in the first character the term begins with and it will display the list in alphabetical order. Use the mouse or the down arrow button to navigate to the correct term. Press enter or click the left mouse button to select the term. If the correct term is not available use an appropriate alternative instead. Usually, new pharmaceutical form terms can be required in advance by the agency responsible to run the procedure of the new marketing authorisation application. Strength(s) The strength(s) will be entered in a structured way. Consider regulatory requirements relating to the rules on naming of combination products. The units of measurement are selected from a controlled list according to standard terms as provided by EDQM (For selection the term name its first character is being used to display the list). The active ingredient data fields need to be duplicated as necessary. Page 23 of 80

24 Active Substance(s) Use the drop-down menu to select the active substance. The dropdown menu also includes a dictionary. Type in minimum of three characters from the name of the active substance name and click search. Enter more characters to receive more accurate results. Scroll through the list or use the arrow-downbutton of the keyboard and select the correct name. Confirm the selection by clicking OK. The selected substance name will be displayed. Click the OK button to close the section. For corrections Add Active Substances needs to be activated and opens the dialogue again. To select another active substance, click in the add new substance section and open the dialogue by clicking Add Active Substances. Do this for each additional active substance. The example above displays the case of two active substances. Once the list is complete click Populate data to copy to all similar sections. Page 24 of 80

25 Note: Other similar sections cannot be filled if this first one is not completely populated. Note: Workaround solution for entering formatted text using rtf format in Word or Outlook and copy pasting the edited text to eaf does not work in the Initial MAA form when the details in sections 2.1.2, and are populated from Declaration section. If you require special characters in these sections, please add an annex and mention this on the cover letter. Select the Populate data in sections 2.1.2, and button and the form will copy data into each respective section with the exception of the Active Substance field in section only. Users need to manually enter, and select an active substance for this field. Base/Active moiety Users may also provide the base/active moiety details of the active substance. This should only be added in this section if different to the active substance, serving to specify the strength of the pharmaceutical preparation and if the substance is included in the product as a salt or hydrate: The class (type) of the substance should be selected from the proposed catalogue. Applicant The applicant address details should be selected from SPOR OMS organization dictionary as outlined in the Providing OMS details section. Page 25 of 80

26 One of the address lines presented can be selected and its selection need to be confirmed by clicking Select or Select/Close. All available details will be retrieved from OMS: Page 26 of 80

27 Personal details like telephone and address are not available in OMS and need to be added as appropriate. Person confirming fees will be/ have been paid, on behalf of the Applicant The following fields must be completed in accordance to the letter of authorisation as detailed in the user guidance available for human medicinal products at CMDh and for veterinary medicinal products at CMDv.CMDv. However, the company address details can be copied from the previous section by clicking the Copy contact details button from previous section button. 1. Type of application The following examples describe the options to complete the form according to the planned procedure. Selecting one of the round boxes will add further lines while changing the selection will hide the lines as appropriate for the respective procedure.. Page 27 of 80

28 1.1. This application concerns In this case the centralised procedure is selected as an example how the section will be expanded depending from the selected procedure type. This example is for human products specifically, for details of the veterinary products application form, please follow the link. The CAT-Rapporteur is only assigned in case of Combined Advanced Therapy Medicinal Products. In other cases, the selection of rapporteurs will be adjusted as appropriate. This example is for veterinary products only: Page 28 of 80

29 A Centralised Procedure For extension applications as indicated in section 1.3, if the corresponding original eligibility basis no longer exists. Only a Centralised Procedure should be indicated, leaving the eligibility basis tick boxes blank. The eaf does not support this very rare case of difference as details of the CHMP acceptance are required due to validation rules. (A workaround might be explained in the Q&A document if necessary.) A Mutual Recognition Procedure For a mutual recognition procedure, the Reference Member State and details of that national authorisation need to be added. Concerned Member States can be added line by line or all in one go. Type in the first character of the Member States name. Or use the down the drop-down menu. Click the + button for a next line or hit return to confirm the selection. Page 29 of 80

30 In case of Repeat -use Procedure the list is indicated as first wave. A second wave will be added by +.at the right upper corner A Decentralised Procedure There is no specific technical information to be considered A National Procedure There is no specific technical information to be considered. Page 30 of 80

31 1.2. Orphan Medicinal Product Information (human only) If your product is an orphan medicinal product, provide the below details. Tick Yes to display the data fields: 1.3. Application for a change to existing marketing authorisation leading to an extension as referred to in Annex I of Regulation (EC) no 1234/2008, or any national legislation, where applicable? There is no specific technical information to be considered This application is submitted in accordance with the following article in Directive 2001/83/EC as amended There is no specific technical information to be considered Consideration of this application requested under the following article of Directive 2001/83/EC or Regulation (EC) No 726/2004 There is no specific technical information to be considered. Page 31 of 80

32 1.6. Requirements according to Regulation (EC) N 1901/2006 ( Paediatric Regulation ) There is no specific technical information to be considered. 2. Marketing Authorisation Application 2.1. Names(s) and ATC code Proposed (invented) name of the medicinal product in the European Union / Member State/Iceland/Lichtenstein/ Norway The information is identical to the one in section Declaration and signature and has to be populated automatically (see Section 1.1.1). If the box is ticked like this an Annex 5.19 need to be provided. This field appears only in case of MRP or DCP selected in section 1.2 or 1.3. The annex is not integrated into the form but the required list should be added as a separate PDF file to the submission. Attachments to the form should be included as per the currently approved processes. Annexes to the application form should always be included in section 1.2 of EU Module Active substance(s) The declaration of the active substance is populated automatically if the button in section 1 has been clicked. Any changes you want to apply must to be executed in section 1 first and this in turn correctly populates this section. Page 32 of 80

33 Correct substance name or strength in section Declaration and Signature to be displayed in this section correctly. Section being populated with above mentioned details: Ibucafego 200 mg / 20mg Page 33 of 80

34 Pharmacotherapeutic group The most complete code corresponding to the claimed therapeutic use of the product should be given. Please use current ATC codes. Consequently, this section should be duplicated where needed. To display the list, at least three characters need to be inserted. The list starts with the next available code based on your entry. The two fields ATC Code and Group are linked and should be both completed. Select for ATC Code field from the lowest level. Select for Group field from the third or fourth level description. Note: The group text field is limited. You may have to reduce the text appropriately. It is advisable to know the ATC code in advance as the search tool does display displaying the entire details of each code Strength, pharmaceutical form, route of administration, container and pack sizes Strength and pharmaceutical form (use current list of standard terms European Pharmacopeia) If the values of the Pharmaceutical form, Strength and Active Substance field have been populated from the Declaration section it is not possible to edit the following data fields. If you need to correct an error, go back to Declaration section. Page 34 of 80

35 Search and select the active substance(s) in the Declaration section and populate the sections where active substance is required by clicking Populate data in section and If a salt/ester/maleate/monohydrate etc. form is required, this can be added via the corresponding base/active moiety field as detailed in Base/Active moiety section Route(s) of administration (current list standard terms - European Pharmacopoeia) Use the dropdown field to open the search menu. The dropdown includes the current list of standard terms included in the List of Standard Terms for pharmaceutical dosage forms, routes of administration and containers published by the EDQM / RMS. Repeat the routes field using the + and/or - buttons. Page 35 of 80

36 Container, closure and administration device(s) Include a description of material from which it is constructed. Use the current list of standard terms - European Pharmacopoeia. Provide details for each of the pack sizes that are planned for marketing. The package sizes fields are can be repeated using the + / - button. The material field is a free text but it is advisable to use known standard abbreviations for chemical names, such PVC or HDPE. Page 36 of 80

37 These are numeric fields, where. as a decimal separator needs t b d Medical Devices The medical product incorporates, as an integral part, one or more medical devices within the meaning of Article 1(2)(a) of Directive 93/42/EEC or one or more active implantable medical devices within the meaning of Article 1(2)(c) of Directive 90/385/EEC. There is no specific technical information to be considered Legal status The dispensing status applies to all Member States the product is authorised to be marketed. For convenience all Member States selected according to section 1.1 can be added or removed by clicking the Add Selected or Remove All buttons. Page 37 of 80

38 The button Add All should not be used as in that case the RMS will not be added. The adjustment of the list can easily be achieved by deleting single Member States clicking the - button Marketing authorisation holder / contact persons / company Select from 2 options: Centralised Procedure and National Procedures in section 1.1. It is not possible to change the selection in this section. Copy address details from the Declaration section by clicking on one of the following buttons Proposed responsible marketing authorisation holder/person Page 38 of 80

39 In the second case the address details will be assigned to the respective Member State. To simplify data entry a button to insert contact details from Declaration section is available. To add the Member States selected in that section click Add Selected. Page 39 of 80

40 For MRP/DCP/National procedure; The Member State field allows multiple Member States to have the same marketing authorisation holder contact person, or alternatively to show that one or more Member States have different marketing authorisation holder contact persons. Note: This field is not mandatory and it will be expected that all relevant member states have the same marketing authorisation holder contact person. Additionally, details of proof of payment can be entered regardless of the procedure. If the fees have not been paid in advance and an invoice is going to be sent select No and indicate the billing address (even if it has not yet been relevant to pay a fee as it will be invoiced later). For a Centralised Procedure; either select EU from the term list or leave the Member state field empty Person/company authorised for communication on behalf of the applicant during the procedure No specific technical guidance is necessary. Page 40 of 80

41 Person/company authorised for communication No specific technical guidance is necessary Summary of the applicant pharmacovigilance system For the section Summary of the pharmacovigilance system, in a community procedure with more than 1 MAH Qualified Person in EEA for Pharmacovigilance can be increased for more than one QPPV. Also the location of the Pharmacovigilance system master file can be multiplied independently. If the location is the same for all Member States, the Member states need to be added in the first box. If this is not the case, the entire section needs to be copied. In this case section needs to be repeated as different PV master files will be maintained. For each system the QPPV may be identical Manufacturers Note: All manufacturing and control sites mentioned throughout the entire dossier must be consistent regarding names, detailed addresses and activities. In this section the address fields offer a possibility to enter two addresses if the administrative address differs from the manufacturing site: Authorised manufacturer(s) (or importer(s)) responsible for batch release in the EEA Subsections are defined to describe different roles: Authorised manufacturer(s) (or importer(s)) responsible for batch release in the EEA in accordance with Article 40 and Article 51 of Directive 2001/83/EC ( as shown in the package leaflet and where applicable in the labelling or Annex II of the Commission Decision) Official batch release for Blood products and Vaccines Details of the Official Medicines Control Laboratory (OMCL) or laboratory designated for the purpose of official batch release (in accordance with Articles 111(1), 113, 114(1)-(2) and 115 of Directive 2001/83/EC as amended) Contact person in the EEA for product defects and recalls Batch control Testing arrangements On top of the sub-section a free text field is available so applicants who have multiple manufacturers doing batch releases can include details of, for example, which packaging the manufacturer is responsible for. This is an optional field that can be left blank it is not required. The following screens illustrate the principle of the two options offered for all address fields in section 2.5 in case the administrative address and the manufacturing facility address is identical or different: Option # 1:- Administrative and manufacture address(es) are the same The fields related to telephone, can be duplicated in order to indicate more than one number in in case the administrative and operating addresses differ: Page 41 of 80

42 Option # 2:- When the administrative address and manufacture address are different: For additional authorised manufacturer s data fields can be repeated, where required, using the + / - buttons: Any manufacturer responsible for batch release in the EEA should be listed under section of the application form. This is the only section where this information should be provided. If the site responsible for batch release in the EEA is also involved in batch control testing activities, the name and address of such site should be repeated in section Page 42 of 80

43 Repeat this sub-section as many as manufacturing facilities must be entered Manufacturer(s) of the medicinal product and site(s) of manufacture A free text field is included to add a description of the partial product (e.g. vial with solvent, vial with powder, solvent etc. can be included to indicate which part of the product a specific manufacturer produces. This field is optional. Page 43 of 80

44 Address details can be copied from section a if identical or if it is more convenient to make minor corrections afterwards. For sites in the EEA, the manufacturing authorisation number should always be provided. In addition, either a copy of the authorisation (tick box) or the EudraGMDP reference number should be provided. If neither the copy nor the EudraGMDP number are provided a validation error is displayed. Note: Including manufacturing sites of any diluent/solvent presented in a separate container but forming part of the medicinal product, quality control/ in-process testing sites, immediate and outer packaging and importer(s). For each site provide the relevant information. If the site is outside the EEA provide the following information: Page 44 of 80

45 In case In the case company the company address or just the address address or just details the of manufacturing address sites details needs of to be multiplied, manufacturing the address sites or the address needs details to of be the manufacturing multiplied, site can the be duplicated address maintaining or the the one address address of the details administrative of the site: manufacturing site secti 2.5. Regarding section (Manufacturer of the medicinal (Manufacturer of the medicinal product) and and (Manufacturer (Manufacturer of the active of substance) the active the substance) manufacturer the names, manufacturer addresses names, and in addresses case manufacturing and case sites manufacturing need to be stated sites (and need repeated) to be stated in each (and section repeated) separately. in each To section separately. To avoid avoid duplication of data entry, duplication of data entry, the the buttons are offered: buttons are offered: The reasoning from a regulatory point of view reads as follows: Release testing of the finished product is part of Quality testing. This activity is only linked to sites performing Batch Control testing arrangements in relation to the Batch Release of the product as per requirements of Article 51 of Directive 2001/83/EC. As such a site may perform both release testing under and normal QC- FP activities under which are not linked to the batch release. In this case, the site(s) will be listed twice i.e. under each section. However, if the site only performs one or the other quality control testing only, the site(s) will then need to be listed in the relevant section depending on the QC-FP activity. Testing arrangements in relation to the Batch Release of the product. Sometimes, sites perform both kinds of testing activities however only sites located in the EEA or where an MRA or ACAA arrangement is in place can be listed in Third country sites (USA and any other country outside the EEA/MRA/ACAA) cannot perform this activity and should therefore not be listed These sites are only authorised to perform QC-FP activities not related to the Batch Release. However, only the tests carried out for the products in the application should be listed here. Therefore, you should not mention all possibilities as is stated in Manufacture License for company (if possible to find them there). Page 45 of 80

46 Manufacturer(s) of the active substance(s) and site(s) of manufacture All manufacturing sites involved in the manufacturing process of each source of active substance. For each site provide the relevant information. The active substance is selected from previously selected list (Section 2.1). The values of Active Substance field have been populated from Declaration section. Page 46 of 80

47 Use the drop-down menu to select between the manufacturing steps performed. The dictionary for processing of medicinal products and for manufacturing steps are linked to the guidance document included in the eaf itself next to this field where more information can be sought from. These are the Interpretation Documents for MIAs and GMP certificates. These are part of the Compilation of Union Procedures on Inspections and Exchange of Information, which is published on the EMA external website (see pages )1. E.g. the role Manufacture of the finished product or Manufacturing of the VMP are covered by the term Processing of medicinal product The contents of the controlled vocabulary are coming directly EUTCT (for substances only) as well as RMS (for all other lists) and the terms have been decided by the European inspectors from documents issued from Inspection. Additional information in regard to inspections, suitability of Pharm. Eur. Certificates or information on ASMF can be entered if the respective box yes is ticked. 1) pdf Page 47 of 80

48 Contract companies used for clinical trial(s) (including bioavailability and bioequivalence studies) included in the application or used for the validation of blood product manufacturing processes. For each contract company, state where analytical tests are performed and where clinical data is collected and open data fields by clicking the Add Study button. Page 48 of 80

49 In cases where multiple studies have been performed by only one contract company all study titles can be keyed in by repeating the first section. Company details are grouped and details of the tasks related to the study can be provided. In case multiple contract companies have been involved the address fields and details of the tasks can be repeated using the + / - buttons Quantitative and Qualitative Composition Qualitative and Quantitative composition in terms of the active substance(s) and the excipient(s) The chosen active substance(s) is/are automatically displayed in section on the Name of active substance field(s). Additional information on the active substance including all excipients in a separate list can be added. To interpret the composition correctly the reference of counting must be stated in the first line. All quantities of substances are referring to a defined quantity of the specified pharmaceutical form, e.g. 1 (unit) of tablets or 100 (ml) of a solution. Page 49 of 80

50 Press this button to duplicate the section for an additional strength (CP only) Free text field for additional description or qualifying Free text field for additional description or qualifying In centralised procedures multiple strengths can be included on one application form. For this purpose the following frame of strength needs to be duplicated. In case of national procedures only 1 strength per pharmaceutical form can be mentioned in 1 MAA form. In the free text field, add a qualifying like calculated as. This text field will also serve for an additional explanation to separate the filling of a capsule from the capsule shell or clustering all ingredients of the printing ink. The quantity is built with an operator, a value and the unit of measure: equal to 20 mg. A reference can also be added, e.g. Pharm.Eur. If you select range as the quantity operator, the value field will be split into a lower and upper value. The quantity operator quantity sufficient is defined as adding enough of an ingredient to achieve a specific final volume or total weight. This term has been discussed extensively in the past and it was Page 50 of 80

51 agreed that quantity sufficient was introduced as quantity operator in the eafs to describe the limits precisely. To express for example: to five grams of NaCl add enough (quantity sufficient qs) water to make 100 ml Ingredient = water Quantity operator = quantity sufficient ; Value =100 Unit = ml If multiple active substances have been selected in the Declaration section, these are automatically displayed. Delete any unnecessary fields displaying incorrect terms using button. Process steps in case of a missing substance name/term If you need to request a missing substance to complete an eaf, submit a request for substance insertion with the corresponding SmPC using the EMA Service Desk portal. To request a new term (e.g. pharmaceutical form or unit of measurement) or a request for an update of an existing term in order to complete the eaf, please submit a request through the SPOR Portal and provide as much supporting documentation as possible (e.g. name of the product concerned, SmPC, etc.). Please note you need to be registered with SPOR prior to submission of change requests: The user guide for managing referential and organisation data in eaf is available here. A provisional term may be added to the list within 5 working days; however, please note that there is a possibility that the term might not be approved in future. More information on how to request additional terms in eaf can be found in the RMS Web User Manual available here. In case of declaration of overages it is mandatory to complete this section: Page 51 of 80

52 Press the + button and select from the drop-down menu the substance as included in the composition then add the overage value. Use a full stop to indicate decimal numeric values List of materials of animal and/or human origin contained/ used in the manufacturing process of the medicinal product? There is no specific technical information to be considered Is an EMEA certificate for a Plasma Master File (PMF) issued or submitted in accordance with Directive 2001/83/EC Annex I, Part III, being used for this MAA? There is no specific technical information to be considered Does the medicinal product contain or consist of Genetically Modified Organisms (GMOs) within the meaning of Directive 2001/18/EC? There is no specific technical information to be considered. 3. Scientific advice 3.1. Was there formal scientific advice(s) given by EMA for this medicinal product? There is no specific technical information to be considered Was there scientific advice(s) given by Member State(s) for this medicinal product? These sections may be replicated where needed. 4. Other marketing authorisation applications There is no specific technical information to be considered. 5. Annexed documents (where appropriate) There is no specific technical information to be considered. Page 52 of 80

53 MAA FORM (veterinary) On the following pages, technical information with regards to the veterinary marketing authorisation application form is provided. To avoid duplication of information reference is provided to the human MAA form as appropriate. Information related to the variation and renewal form will be provided in a separate section thereafter. Administrative data For details on this section please refer to the identical section of the MAA form for human medicinal products. Declaration and signature The following example is provided to illustrate some principles in this section which are entirely the same human medicinal products. Page 53 of 80

54 1. Type of application The following examples describe the options to complete the form according to the planned procedure. Ticking one of the round boxes will add further lines as appropriate for the respective procedure. Changing of the selection will hide the lines but addition different ones according to the other procedure selected This application concerns In this case the centralised procedure is selected as an example how the section will be expanded depending from the selected procedure type. This example is for veterinary products specifically, for details of the human products application form, please follow the link A Centralised Procedure There is no specific technical information to be considered A Mutual Recognition Procedure There is no specific technical information to be considered A Decentralised Procedure There is no specific technical information to be considered. Page 54 of 80

55 A National Procedure There is no specific technical information to be considered Is this an application for a change to your existing marketing authorisation leading to an extension as referred to in Annex I of Regulation (EC) NO 1234/2008, or any national legislation, where applicable? There is no specific technical information to be considered This application is submitted in accordance with the following articles in Directive 2001/82/EC There is no specific technical information to be considered MRL status (only for food-producing species) Page 55 of 80

56 Page 56 of 80

57 The form requires excipients not included in Regulation (EU) No 37/2010 should also be listed and an appropriate justification given. If this is the case, tick not applicable and provide justification in the remarks field. In case an MRL application has been submitted to the EMA and the procedure is still pending, tick Yes and provide details on the application including submission date in this section: 1.5. Consideration of this application is also requested under the following article in Directive 2001/82/EC or Regulation (EC) No 726/2004 There is no specific technical information to be considered. 2. Marketing authorisation application particulars 2.1. Name(s) and ATC vet code and target species Proposed (invented) name of the veterinary medicinal product in the European Union / Member State/Iceland/Lichtenstein/ Norway The information is identical to the Declaration and signature and is populated automatically. If the box is ticked provide Annex This field is only displayed in the case of an MRP or DCP selected in section 1.2 or 1.3. The annex is not integrated into the form but added as a required list in a separate PDF file to the submission Active substance(s) The declaration of the active substance is populated automatically if the button in section 1 is clicked. Page 57 of 80

58 Pharmacotherapeutic group (Please use current ATC vet code) Target species The most complete code corresponding to the claimed therapeutic use of the product should be given. Consequently, this section should be duplicated where needed. The ATC Code (select vet specific terms) and Group fields are linked and both should be completed. It is recommended to key in the third or fourth level description. However, the description of the third or fourth level of the ATC vet code may be too long to include completely Strength, pharmaceutical form, route of administration, container and pack sizes Strength and pharmaceutical form (use current list of standard terms European Pharmacopeia) For details refer to the human products application form Route(s) of administration (use current list of standard terms - European Pharmacopoeia) The drop-down menu includes the current list of standard terms included in the List of Standard Terms for pharmaceutical dosage forms, routes of administration and containers published by the EDQM / RMS. Repeat the routes if required using the + / - buttons. Complete the section by selecting the target species again. Page 58 of 80

59 Container, closure and administration device(s), including description of material from which it is constructed. (use current list of standard terms - European Pharmacopoeia) Provide details for each of the pack sizes planned for marketing. Repeat the package sizes fields if required using the + / - buttons as displayed in the example above. In this example highlighted fields indicate the mandatory section to be input as a minimum. The highlight appears after clicking the validate form button at the end of the form. The term list on Container, Closure and Administration Device will become more complete over time. Therefore, check carefully in advance whether the term you will use is provided. Otherwise, request the term as soon as possible at mdms@ema.europa.eu. The material is a free text field, but it is advisable to use known standard abbreviations for chemical names, such PVC, HDPE, etc. Page 59 of 80

60 2.3. Legal status There is no specific technical information to be considered Marketing authorisation holder / contact persons / company For details refer to the human products application form Manufacturers For details refer to the human products application form Quantitative and qualitative composition Qualitative and Quantitative composition in terms of the active substance(s) and the excipient(s) For details refer to the human products application form List of materials of animal and/or human origin contained or used in the manufacturing process of the medicinal product? There is no specific technical information to be considered Does the veterinary medicinal product contain or consist of Genetically Modified Organisms (GMOs) within the meaning of Directive 2001/18/EC? There is no specific technical information to be considered. 3. Scientific advice 3.1. Was there formal scientific advice(s) given by CVMP for this veterinary medicinal product? There is no specific technical information to be considered Was a scientific recommendation(s) given by Member State(s) for this veterinary medicinal product? These sections may be replicated if needed. 4. Other marketing authorisation applications There is no specific technical information to be considered. 5. Annexed documents (where appropriate) There is no specific technical information to be considered. Page 60 of 80

61 VARIATION FORM On the following pages technical information on the variation form is provided. 1. Application for variation to a marketing authorisation Details of the procedure number and involved Member States depend from the type of procedure. In case of variations to a national authorisation in MRP/DCP select the Reference Member State. In the list below all Member States or the EMA can be selected except the same Member States as already selected in the role of RMS. You may add member states line by line or click Add all to add all member states at once. To remove them all in one go by click Remove all. It is also possible to remove single member states line by line. Page 61 of 80

62 Select the type of variation next. In case of variations other than IA/IAIN additional information about the scope of the variation should be indicated. Additional information on the scope is requested. In case of purely nationally authorised products involved in a work sharing procedure, the Reference Authority will be included instead of the RMS. The selection of the MA Holder address will be supported by the SPOR Organisation Management Service as outlined in providing contact & address details. 2. Products concerned by this application The variation form allows you to include all forms and strengths. Again, the signatures should be provided by the MAH. If different national companies are involved it is recommended to add power of attorney as required by member states appropriately. The products involved in the variation need to be named. To allow all possibilities to be keyed in within a structured manner, this section has completely been revised. The principles of that construct are explained in the following example: Page 62 of 80

63 The sample displays how several products with different authorisation numbers different product names or different MAH names etc. can be added. In case the strength details are too complex, a footnote can be added to describe the strengths in more detail: Page 63 of 80

64 3. Types(s) of changes (s) You have to confirm that all relevant pages from the Guideline will be added as well as the relevant documentation by ticking the check box: The classification Guideline table should be added as a separate document provided in the same location as the application form, clearly identifiable as Classification Guideline. File name could be common-formannex-classgl.pdf. It is important not to attach the annexes into the eaf as it will prevent proper locking of the forms The next step is to select the changes you want to submit: The full list of variation items according to EU Commission Guidelines will be displayed by clicking Show All Types. Once you have made your selection you can close the list /collapse the list to show only the selected items by clicking Show Only Selected/Collapse All at the end of the list. You may control the selection and adjust it. To correct the list click Refresh Selected. List of selected items Page 64 of 80

65 Deselected items Updated list after pressing the refresh button Depending from the items you have to complete, the following table describes the present and proposed wording in the PL or SmPC or any brief description of the changes, or DUNS number of involved manufacturer or ASMF reference number. Due to the anticipated complexity this is not needed in case of work sharing or grouping procedures affecting more than one product. It is mandatory to select at least one scope from the list. Page 65 of 80

66 Present and proposed section text fields It is possible to include formatted text, but only in the present and proposed text fields of this form. All other free text fields in the forms allow only plain text. Track-changes functionality is currently not available in interactive Acrobat forms. The formatting can be changed based on the following rules: Using the right mouse button, you can select Text style providing the same options: If selecting Hyperlink, the pop-up will provide more options to directly format the text or paragraph: Page 66 of 80

67 Alternatively, rich text (formatted) can be used by editing the text in Word or Outlook in the rtf format. Copy and paste the formatted text in to the present and proposed fields. A complex table as part of the present and proposed section in the variation eaf cannot be included. When a table is needed in the present and proposed section of the eaf you are able to include the information in separate annex included in folder 1.2 of the ectd structure for Human applications or in the 1a-admin-info folder of the VNeeS structure for Veterinary applications. The annex should be attached as a separate PDF document, clearly named (for example ema-formannex-presentandproposed ) in the folder 1.2 or folder 1a-admin-info for VNeeS submissions. Text such as 'See Annex Present and Proposed' should be entered into the mandatory present and proposed fields of the eaf. To include an image (always one image per cell) click the left mouse button into the cell. Select from your file share an image as appropriate. If the size needs to be adjusted, please provide the image as an annex as the image cannot be enlarged. Additionally, it is not possible within one section of the present/proposed table to alternate text fields and image fields. You will need to repeat the scope section entirely. Present and proposed section address details The section now allows the usage of OMS entry. Page 67 of 80

68 Depending on the role of the company of which the address needs to be included, it may happen that OMS cannot provide details. It is assumed that in those cases more likely in the present part of that section the details need to be completed manually. Although due to the early stage of productive OMS usage not every address might be available, it is highly recommended to use OMS for any new address to be inserted in the proposed section. 4.a Type IB and Type II variations new indications orphan medicinal product information This section is only displayed if variation type IB or type II has been selected. The section can be flagged out, if not applicable: Page 68 of 80

69 4.b Type IB and Type II variations Paediatric Requirements This section is only displayed if variation type IB or type II has been selected. This section can be flagged out, if not applicable Page 69 of 80

70 4.c Type II variations Extended data exclusivity/market protection This section is only displayed if variation type II has been selected. The section can be flagged out, if not applicable Page 70 of 80

71 Annexed documents (where appropriate) Declaration of the applicant Signature Complete these sections in the same way as previous forms. 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0) Facsimile +44 (0) Send a question via our website An agency of the European Union European Medicines Agency, Reproduction is authorised provided the source is acknowledged.

72 RENEWAL FROM 1. Application form for renewal of a marketing authorisation This form is applicable to both domains and you have to make a selection at first (indicated with arrows in the figure below): All member states can be included in one go. + for an additional invented name + for an additionalpharmaceutical d A renewal form must be provided for each form and strength of a medicinal product (except for Centrally Authorised products where renewal always covers the whole product with all its forms and strengths). Nevertheless, the product name per member state may differ. In case of combined packages and different composition of pharmaceutical products need to be addressed, several options to copy data fields are provided. Another difference to the previous form is the indication whether the product is marketed or not (squared box), but all other details need to be completed as known from the MAA form or the variation form. Again you have the option to populate the product details in section Qualitative and quantitative composition (section 3.) Provide further product characteristics: Page 72/80

73 When selecting Veterinary this section is adapted to add the target species and it is likely the ATC vet code and respective group are chosen (although not explicitly mentioned): The name and address of the Marketing Authorisation Holder will be handled in the same way as in other forms. Page 73/80

74 Again buttons are added to allow replication of data: 2. Approved manufacturers Page 74/80

75 Details of the role of the manufacturer can be described in the free text field on top. Page 75/80

76 The free text field can be used to indicate the role of the manufacturer for applications with multiple active substances, excipients and manufacturers. For example, this field can be used to indicate the manufacturer of the Drug product and manufacturer of the solvent or the batch release of the product. Leave this field blank if not required. In the various address fields you will find buttons to copy the address details as appropriate. Page 76/80

77 Ph. Eur certificate has been issued, further details can be provided in this section. If 3. Quantitative and qualitative composition in terms of the active substance(s) and the excipient(s) This section is concluded with a tabular listing of changes of the product information texts. This table can be provided as a separate document attached to the application form as well. Per section or subsection of the SmPC or PL you should use a separate line item by item to be changed. Page 77/80

78 If you formatted text is to be used follow the tips provided here. 4. Documents appended to this application In cases where a renewal is being made for either a human or veterinary medicinal product following the nationally authorised procedure (National authorisation in MRP/DCP or National authorisation only), users can elect to have a shortened renewal procedure and provide the appropriate justification as displayed below: For the remaining Module 1 section, depending on your selections, complete the list of documents you will attach. Page 78/80